Evaluation of the introduction of novel potassium binders in routine care; the Stockholm CREAtinine measurements (SCREAM) project

Abstract

Background: The pharmacological management of hyperkalemia traditionally considered calcium or sodium polystyrene sulfonate and, since recently, the novel binders patiromer and sodium zirconium cyclosilicate. We evaluated their patterns of use, duration of treatment and relative effectiveness/safety in Swedish routine care.

Methods: Observational study of adults initiating therapy with sodium polystyrene sulfonate or a novel binder (sodium zirconium cyclosilicate or patiromer) in Stockholm 2019-2021. We quantified treatment duration by repeated dispensations, compared mean achieved potassium concentration within 60 days, and potential adverse events between treatments.

Results: A total of 1879 adults started treatment with sodium polystyrene sulfonate, and 147 with novel binders (n = 41 patiromer and n = 106 sodium zirconium cyclosilicate). Potassium at baseline for all treatments was 5.7 mmol/L. Sodium polystyrene sulfonate patients stayed on treatment a mean of 61 days (14% filled ≥3 consecutive prescriptions) compared to 109 days on treatment (49% filled ≥3 prescriptions) for novel binders. After 15 days of treatment, potassium similarly decreased to 4.6 (SD 0.6) and 4.8 (SD 0.6) mmol/L in the sodium polystyrene sulfonate and novel binder groups, respectively, and was maintained over the 60 days post-treatment. In multivariable regression, the odds ratio for novel binders (vs sodium polystyrene sulfonate) in reaching potassium ≤ 5.0 mmol/L after 15 days was 0.65 (95% CI 0.38-1.10) and after 60 days 0.89 (95% CI 0.45-1.76). Hypocalcemia, hypokalemia, and initiation of anti-diarrheal/constipation medications were the most-commonly detected adverse events. In multivariable analyses, the OR for these events did not differ between groups.

Conclusion: We observed similar short-term effectiveness and safety for all potassium binders. However, treatment duration was longer for novel binders than for sodium polystyrene sulfonate.

Keywords: Hyperkalemia; Patiromer; SCREAM; Sodium polystyrene sulfonate; Sodium zirconium cyclosilicate.

Fig. 1

Duration of continuous therapy after initiation of potassium binders up to 365 days after treatment initiation by binder type. Legend: Persistence on therapy was estimated based on repeated dispensations for each agent (see methods). P value denotes statistically significant difference in the persistence of SPS vs novel potassium binders, using the log-rank test

Fig. 2

Mean potassium concentration during different intervals after treatment start (panels A and B) and mean potassium change from baseline potassium (panels C and D). Legend: Shown is the mean potassium value closest to the end of each time interval. Panels A and C show each agent separately (SPS, patiromer and SZC), and panels B and D combine both novel potassium binders together. There were no statistically significant differences between treatment strategies (P > 0.05) as estimated by t-test or one-way ANOVA. SPS; sodium polystyrene sulfonate, SZC; sodium zirconium cyclosilicate, Novel K + ; Binder (SZC + patiromer)

Fig. 3

Proportion of patients with plasma potassium concentration ≤ 5.0 mmol/L (Panels A and C) and ≤ 5.5 mmol/L (Panels B and D) before and after initiation of treatment with potassium binders. Legend: Bars (standard error) represent the percentage of patients with potassium ≤ 5.0 mmol/L and ≤ 5.5 mmol/L, modeling the potassium value closest to the end of each time interval. N () shows the number of patients represented in each of the bars. *There were no statistically significant differences between the binders, except for one observation in panel B during the first 15 days of therapy, where Chi² test < 0.05. SPS; sodium polystyrene sulfonate, SZC; sodium zirconium cyclosilicate, Novel K + ; Binder (SZC + patiromer)